全文获取类型
收费全文 | 5447篇 |
免费 | 562篇 |
国内免费 | 452篇 |
出版年
2024年 | 28篇 |
2023年 | 138篇 |
2022年 | 154篇 |
2021年 | 287篇 |
2020年 | 229篇 |
2019年 | 361篇 |
2018年 | 260篇 |
2017年 | 209篇 |
2016年 | 209篇 |
2015年 | 262篇 |
2014年 | 443篇 |
2013年 | 577篇 |
2012年 | 315篇 |
2011年 | 361篇 |
2010年 | 187篇 |
2009年 | 196篇 |
2008年 | 211篇 |
2007年 | 214篇 |
2006年 | 190篇 |
2005年 | 208篇 |
2004年 | 141篇 |
2003年 | 133篇 |
2002年 | 143篇 |
2001年 | 103篇 |
2000年 | 80篇 |
1999年 | 78篇 |
1998年 | 66篇 |
1997年 | 63篇 |
1996年 | 57篇 |
1995年 | 44篇 |
1994年 | 57篇 |
1993年 | 52篇 |
1992年 | 46篇 |
1991年 | 56篇 |
1990年 | 20篇 |
1989年 | 32篇 |
1988年 | 18篇 |
1987年 | 32篇 |
1986年 | 16篇 |
1985年 | 21篇 |
1984年 | 24篇 |
1983年 | 25篇 |
1982年 | 23篇 |
1981年 | 23篇 |
1980年 | 14篇 |
1979年 | 25篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1974年 | 4篇 |
排序方式: 共有6461条查询结果,搜索用时 109 毫秒
101.
Estrogen-stimulation of postconfluent cell accumulation and foci formation of human MCF-7 breast cancer cells 总被引:3,自引:0,他引:3
J F Gierthy D W Lincoln K E Roth S S Bowser J A Bennett L Bradley H W Dickerman 《Journal of cellular biochemistry》1991,45(2):177-187
Foci, nodules of cellular overgrowth, that appear after confluence are an in vitro characteristic of malignant transformation. A well-studied in vitro model of estrogen-dependent tumors is the MCF-7 cell line, derived from a pleural metastasis of a human breast adenocarcinoma. We report that cultivation of MCF-7 cells, using routine methods, results in extensive estrogen-stimulated postconfluent cell accumulation characterized by discrete three-dimensional arrays. Side view Nomarski optical sections revealed these to be principally multicellular foci with occasional domes and pseudoacinar vacuoles. This effect on MCF-7 cell growth occurs in media containing fetal bovine serum but not with calf serum or charcoal-dextran-treated fetal bovine serum unless supplemented with estrogens. Foci formation starts 5-6 days after confluence, and the number of foci generated is a function of the concentration of added estrogens. Foci formation is suppressed by the antiestrogens Tamoxifen and LY 156758. Addition of progesterone, testosterone, or dexamethasone had little or no effect, while various estrogens (ethinyl estradiol, diethylstilbestrol, and moxestrol) induced foci development. Clones derived from single cells of the initial MCF-7 population revealed a wide variance in estrogen-induced foci formation, demonstrating heterogeneity of this tumor cell line. The postconfluent cell growth of the estrogen receptor-deficient cell line, MDA-MB-231, contrasted with MCF-7 by developing an extensive multilayer morphology devoid of discrete structures. The tumorigenic potential of the MCF-7 cells used in our experiments was confirmed by their estrogen-dependent growth in immunosuppressed male BDF1 mice. These data suggest an estrogen receptor-based mechanism for the development of multicellular foci during postconfluent growth of MCF-7 cells. After confluence, foci, in contrast to the quiescent surrounding monolayer, retain proliferating cells. Focus formation, therefore, reflects the heterogeneous responsiveness of these cells to estrogens and should provide a model permitting in vitro comparisons between the progenitor cells of multicellular foci and the monolayer population. 相似文献
102.
Cellular senescence: A reflection of normal growth control,differentiation, or aging? 总被引:6,自引:0,他引:6
Normal cells, with few exceptions, cannot proliferate indefinitely. Cell populations--in vivo and in culture--generally undergo only a limited number of doublings before proliferation invariably and irreversibly ceases. This process has been termed the finite lifespan phenotype or cellular senescence. There is long-standing, albeit indirect, evidence that cellular senescence plays an important role in complex biological processes as diverse as normal growth control, differentiation, development, aging, and tumorigenesis. In recent years, it has been possible to develop a molecular framework for understanding some of the fundamental features of cellular senescence. This framework derives primarily from the physiology, genetics, and molecular biology of cells undergoing senescence in culture. Our understanding of senescence, and the mechanisms that control it, is still in its infancy. Nonetheless, recent data raise some intriguing possibilities regarding potential molecular bases for the links between senescence in culture and normal and abnormal growth control, differentiation, and aging. 相似文献
103.
We have previously demonstrated that the exposure of mouse microvascular endothelium (MME) to tumor necrosis factor-alpha (TNF) led to the increased binding of mouse mastocytoma cells (P815) to endothelial monolayers (Bereta et al., in press). In the current study we examined the possible involvement of protein kinases in TNF signal transduction in the endothelial cells. PKA does not appear to play a role in the potentiation of binding by TNF. We found that the TNF-generated signal is inhibited by H-7 and sangivamycin, but not by staurosporine. TNF did not cause translocation of PKC to the cell membrane and its effect could not be completely mimicked by PMA nor by PMA in the presence of calcium-raising agents. Thus, we concluded that the "classical" PKC pathway is not completely responsible for TNF signalling in this system. We also found that staurosporine itself strongly enhanced adhesion of tumor cells to endothelium, utilizing a mechanism distinct from that of TNF. Although the data provide evidence for the role of kinases in the effect of TNF on binding of tumor cells to MME, this role appears to be a complex one. 相似文献
104.
Henrika G. M. Tiedink Laura H. J. De Haan Wim M. F. Jongen Jan H. Koeman 《Cell biology and toxicology》1991,7(4):371-386
4-chloro-methoxyindole is a naturally occurring compound in Vicia faba which can easily react with nitrite to form a N-nitroso compound. In this in vitro study, the potential genotoxic effects of nitrosated 4-chloro-6-methoxyindole and its structural analogue 4-chloroindole were evaluated for the first time by using both Salmonella and Chinese hamster V79 cells. Additionally, the inhibition of gap junctional intercellular communication in V79 cells by these compounds was determined; this is a validated parameter for tumor-promoting activity. Most assays were also performed with nitrosated indole-3-acetonitrile, a naturally occurring compound in brassicas. Both nitrosated chloroindoles were highly mutagenic to Salmonella typhimurium TA100 without the need of exogenous metabolic activation and were potent inducers of Sister Chromatid Exchanges. Nitrosated indole-3-acetonitrile generated the same effects, although at much higher concentrations. Equivocal results were obtained for the nitrosated chloroindoles in a forward mutation assay using the hypoxanthine guaninephosphoribosyltransferase locus. All nitrosated indole compounds significantly inhibited gap junctional intercellular communication. These results indicate that nitrosated chloroindoles and nitrosated indole-3-acetonitrile should be considered as mutagens and agents with potential tumor-promoting capacity.Abbreviations BrdU
5-bromo-2-deoxyuridine
- 4Cl
4-chloroindole
- 4C6MI
4-chloro-6-methoxy-indole
- DMSO
dimethyl sulfoxide
- EBSS
Earle's balanced salt solution
- EMS
ethyl methanesulfonate
- GJIC
gap junctional intercellular communication
- HBSS
Hanks balanced salt solution
- HGPRT
hypoxanthine guaninephosphoribosyl transferase
- I3A
indole-3-acetonitrile
- MNNG
1-methyl-1-nitroso-3-nitroguanidine
- NOC
N-nitroso compounds
- NQO
4-nitroquinolone-N-oxide
- SCE
sister chromatid exchange
- 6TG
6-thioguanine
- TPA
12-O-tetradecanoylphorbol-13-acetate 相似文献
105.
The circular dichroism (CD) spectrum of tumor necrosis factor-α has been measured into the vacuum UV to 168 nm. Analysis of the CD for secondary structure is in good agreement with X-ray diffraction results, but the analysis is somewhat unstable. Adding the CD of this protein together with its X-ray determined secondary structure to the basis set should improve subsequent analyses of CD spectra for other all-β proteins. 相似文献
106.
Clinical studies with TNF 总被引:4,自引:0,他引:4
107.
108.
The effect of implantation of Ehrlich ascites tumor (EAT) cells of creatine distribution was investigated. It was also studied how depletion of creatine by feeding creatine-analogue β-guanidinopropionic acid (β-GPA) affects the growth of EAT cells in mice. Enhanced mobilization of creatine from host tissues to EAT cells against a greater concentration gradient was observed. The creatine (but not creatinine) level in blood plasma was lowered to 22% of the normal value by β-GPA feeding alone and assimilation of 14C-creatine into EAT cells was inhibited. The growth of EAT cells was significantly reduced and the duration of survival of mice after implantation of EAT cells was extended when the creatine concentration was decreased. A decrease in daily food consumption and the degree of muscle atrophy after implantation of EAT cells was less in β-GPA than control groups. In the creatine-depleted mice, the rate of increase in total EAT cell number and the volume of abdominal ascites were approximately half of the control values, and more dead EAT cells were observed. These results suggest that supplementation of β-GPA inhibits creatine transfer to EAT cells and reduces the growth of cancer cells. 相似文献
109.
Kiyoshi Ohkawa Takashi Hatano Naoko Takizawa Kazue Shinmoto Kyosuke Yamada Makoto Matsuda Koji Takada Yutaka Tsukada 《In vitro cellular & developmental biology. Animal》1992,28(6):449-454
Summary A human yolk sac tumor cell line, TG1, which was established from a testicular yolk sac tumor, was found to replicate continuously
in a chemically defined medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic
antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue polypeptide antigen, transferrin (Tf), epidermal
growth factor, and platelet derived growth factor. By analysis of lectin (LcHA)-affinity electrophoresis, to examine the microheterogeneity
of carbohydrate chains of synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA reactive Tf and AFP based
on core fucose attached to asparagine-linkedN-acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1 cells cultured with fetal bovine serum
(FBS)-containing medium.α1-6 Fucosyltransferase activity was significantly greater in the TG1 cells cultured with ISRPMI (39.9±1.5 pmol · h−1 · mg−1 protein) than cultured with FBS-containing media (18.2±1.2 pmol · h−1 · mg−1 protein). These results have indicated that the selective increase ofα1-6 fucosyltransferase occurred when the cells were cultured with the FBS-free synthetic media. 相似文献
110.